It is the aim of this research program to apply some of the basic knowledge recently obtained in animal models concerning regulation of IgE antibody production to systems designed to analyze in detail various aspects of the mechanisms controlling IgE antibody production in man. A recently developed system for in vitro production of IgE antibodies by peripheral blood lymphocytes of normal humans and individuals with various allergic diseases will be employed to 1) ascertain characteristics of IgE antibody synthesis in different disease states as compared to normals, 2) identify, isolate and analyze mechanisms of action of biologically-active molecules derived from human lymphocytes capable of selectively regulating IgE antibody synthesis, either negatively or positively, by cultured human lymphocytes, 3) develop specific assays for detecting IgE-selective suppressive and enhancing factors in serum of normal and atopic individuals and in supernatants from cultured cells from such individuals, 4) determine correlations between the clinical state of a given individual and the production of, and sensitivity to, IgE-selective immunoregulatory factors, and 5) determine the types of manipulations that may effectively alter production of and/or sensitivity to such IgE-selective regulatory molecules by lymphocytes of normal and atopic individuals, and hence the capacity of such cells to synthesize IgE antibodies in vitro. Moreover, an analysis will be made of the immunoregulatory role that may be played by human lymphocytes bearing specific receptors for the Fc portion of IgE. The information obtained from these studies should add further building blocks necessary for reaching a goal in which responses of the IgE antibody class can be willfully manipulated in an effective therapeutic manner in IgE-mediated allergic diseases and, moreover, perhaps further enlighten our understanding of the fundamental aberrations in IgE antibody synthesis which underlie clinical allergic disorders.